Winfred Chapman Smith, MPH

(404) 752-1140

wsmith@msm.edu

Research Subject Advocate brochure

Since their introduction to Clinical Research Centers (CRCs), Research Subject Advocates (RSAs) have been physicians, nurses, pharmacists, ethicists and other highly trained professionals with relevant research backgrounds charged with ensuring the safety of subjects participating in research in CRC studies. Initial areas of key focus, as guided by NCRR and NIH guidelines in 2001 were to:

1. Guide and assist research staff in creating protocol-specific "Data and Safety Monitoring Plans" (DSMPs) for safety monitoring, AE tracking, and execution of reporting requirements and ensuring that they are implemented;

2. Ensure that the research study is carried out in compliance with the IRB-approved protocol;

3. Ensure that serious adverse events are reported in a timely fashion to the IRB and appropriate federal agencies;

4. Interact with research participants to assess informed consent process and comprehension;

5. If requested by the PI of the CRC, monitor all CRC-based research studies. Over time NCRR guidelines evolved to more global goals, namely "ensuring that research studies are designed and conducted safely and ethically with protection of human subjects the highest priority."

The RSA created a program including education of investigators and research teams as to their ethical and regulatory responsibilities, and provide tools to conduct research optimized to protect human subjects. The RSA also assumes additional roles ranging from review of study design, IRB liaison, membership on IRBs or ethics boards, development of independent safety monitoring programs or committees, direct observation of informed consent, and integration of communication and data sharing across the IRB, the compliance office, CRC, and satellite research sites. The RSA, by the integrative nature of responsibilities, cross the silos of IRB, institutional compliance office, research support services, human subject protection programs, ethics programs, research teams, and research subjects. Extending the RSA model to include entire academic medical institutions in the clinical research enterprise affords an important opportunity to enhance the ethics and safety of the conduct of human subjects' research.

Data Safety and Monitoring

The National Institutes of Health (NIH) policy for data and safety monitoring states that:

• all clinical intervention studies require ongoing oversight and monitoring to ensure the safety of participants and the validity and integrity of data.
• The type of monitoring must be commensurate with the degree of risk, the size, and the complexity of the clinical trial.
• This includes Phase I (physiologic, toxicity and dose-finding), Phase II (efficacy) and Phase III (efficacy, effectiveness and comparative) studies.

The purpose of the Data and Safety Monitoring Process at the Morehouse School of Medicine's Clinical Research Center is:

• to ensure that research is conducted in compliance with the Safety Monitoring Plan approved by the Morehouse School of Medicine's (MSM) Institutional Review Board (IRB), the Clinical Research Centers (CRC) and its Clinical Advisory Committee (CAC).
• The DSMP process prospectively assesses the assumptions made in the protocol design while the study is in progress, and makes recommendations for improving the scientific quality of the clinical trial, while protecting the integrity of human subjects. The CRC Data and Safety Monitoring Process consists of four components:

The process is led by the Data and Safety Monitoring Committee (DSMC) whose primary role and responsibility includes:

• providing the MSM CRC with safety oversight related to compliance with best practice standards required by all IRB, NIH and FDA approved research protocols.

It is anticipated that all Low and Moderate Risk (Level 1) interventional and non-interventional studies, nearly all Moderate Risk (Level 2) non-interventional studies and many Level 2 interventional studies conducted only at the MSM CRC generally will not require DSMCs. A DSMC would be constituted in any large blinded trial considered high-risk to its target population or in a trial studying a vulnerable population. An interim analysis plan and the guidelines for stopping the protocol also will likely be required. Studies requiring DSMCs are almost invariably interventional or gene or cell therapy clinical trials.

The DSMC serves several functions including:

1. to review, evaluate and monitor adverse events occurring in all studies
2. to review protocols identified by the RSA as having potential DSM concerns
3. to serve as a pool of potential External Monitors
4. to make recommendations to the CAC, IRB and CRC Director

The submission of protocols to the MSM/CRC includes a requirement for a mandatory Data and Safety Monitoring Plan (DSMP). CRC Principal Investigators must submit a DSMP as part of the initial CRC research application packet. The DSMP is the responsibility of the Principal Investigator (PI) and is subject to review and approval by the CRC/ CAC and the MSM/ IRB. The CRC RSA will provide technical assistance to the PI in the development of the plan. These plans are stored as part of a file located within the office of the CRC RSA. Each DSMP submitted must include the following:

• Purpose of DSMP
• Risk Category of Protocol (eg. minimal, moderate, high)
• Method of Monitoring and Reporting Adverse Events
• Name of Principal Investigator, Co-Investigators and other Research Team
• Brief Description of the study (eg. Study Goals and Hypothesis, Study Population etc.)
• Confirmation of NIH and MSM Ethics Course Completion
• Method of documenting and reporting Adverse Events